TY - JOUR
T1 - GPR107, a G-protein-coupled receptor essential for intoxication by Pseudomonas aeruginosa exotoxin a, localizes to the Golgi and is cleaved by furin
AU - Tafesse, Fikadu G.
AU - Guimaraes, Carla P.
AU - Maruyama, Takeshi
AU - Carette, Jan E.
AU - Lory, Stephen
AU - Brummelkamp, Thijn R.
AU - Ploegh, Hidde L.
PY - 2014
Y1 - 2014
N2 - A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport.
AB - A number of toxins, including exotoxin A (PE) of Pseudomonas aeruginosa, kill cells by inhibiting protein synthesis. PE kills by ADP-ribosylation of the translation elongation factor 2, but many of the host factors required for entry, membrane translocation, and intracellular transport remain to be elucidated. A genome-wide genetic screen in human KBM7 cells was performed to uncover host factors used by PE, several of which were confirmed by CRISPR/Cas9-gene editing in a different cell type. Several proteins not previously implicated in the PE intoxication pathway were identified, including GPR107, an orphan G-protein-coupled receptor. GPR107 localizes to the trans-Golgi network and is essential for retrograde transport. It is cleaved by the endoprotease furin, and a disulfide bond connects the two cleaved fragments. Compromising this association affects the function of GPR107. The N-terminal region of GPR107 is critical for its biological function. GPR107 might be one of the long-sought receptors that associates with G-proteins to regulate intracellular vesicular transport.
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U2 - 10.1074/jbc.M114.589275
DO - 10.1074/jbc.M114.589275
M3 - Article
C2 - 25031321
AN - SCOPUS:84906875898
SN - 0021-9258
VL - 289
SP - 24005
EP - 24018
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 35
ER -